No abstract

No abstract

OBJECTIVE: Partial and complete hydatidiform moles (PHM, CHM) are a common cause of pregnancy loss. To assess the frequency and nature of genomic imbalances, specifically polyploidy resulting in PHM and whole-genome uniparental disomy (WG-UPD) resulting in CHM, a comprehensive analysis of a large cohort of miscarriage samples was analyzed by single nucleotide polymorphism (SNP)-based chromosomal microarray (CMA). STUDY DESIGN: The CMA results for 21,342 miscarriage samples were analyzed for polyploidy and WG-UPD. DNA extracted from fresh products of conception (80%) or formalin-fixed paraffin embedded samples (FFPE, 19%) were subjected to SNP-based CMA. When available, correlation with histopathology was attempted. RESULTS: Abnormal CMA results were observed in 55.7% (11,899/ 21,342) of samples. Of these 11,899 cases, polyploidy was identified in 1641 (13.8%) and WG-UPD in 150 (1.26%). Majority of polyploid samples (1631/1641) had triploidy, of which 216 had hyper-or hypotriploidy, and 10 had confirmed or possible tetraploidy. SNP-genotype data suggested 6/150 CHM samples with WG-UPD resulted from dispermy. Histopathology was suggestive of PHM or CHM in only 236 samples (1.1%); 186 of these (79%) had abnormal CMA results (67 with polyploidy, 70 with WG-UPD) and the remainder with aneuploidy. Histopathology was more often suggestive of molar pregnancy in cases with WG-UPD (54/150, 36%) compared to polyploidy (60/1641, 3.7%). CONCLUSION: Diagnosis of polyploidy and whole-genome UPD as a cause of pregnancy loss is challenging. Implementation of SNP-based CMA provides a powerful tool enabling accurate identification of polyploidy and WG-UPD. The accurate genetic classification of PHM and CHM underscores the immense value of a genotype-first approach for accurate detection of molar pregnancies, and in particular for the identification of PHM that are unsuspected by histopathology. This study provides a comprehensive estimate of the frequency and types of genomic abnormalities that impact trophoblastic transformation of conceptions and result in partial or complete hydatidiform moles.

No abstract